Exploiting innovative sensing mechanisms and their rational implementation for selective and sensitive detection has recently become one of the mainstream research directions of photoelectrochemical (PEC) bioanalysis. In contrast to existing conventional strategies, this study presents a new liposome-mediated method via in situ combining ZnInS nanosheets (ZIS NSs) with SnS2 to form a ZIS NSs/SnS2 type-I heterojunction on fluorine-doped tin oxide (FTO) electrodes for highly sensitive PEC immunoassays. Specifically, alkaline phosphatase (ALP)-encapsulated liposomes were confined within 96-well plates by sandwich immunorecognition and subsequently subjected to lysis treatment. Enzymatically produced H2S by the released ALP was then directed to react with Sn(IV) to engender the ZIS NSs/SnS2 type-I heterojunction on the FTO/ZIS NSs-Sn(IV) electrode, resulting in a change in the photogenerated electron-hole transfer path of the photoelectrode and reduction in current signaling. Exemplified by heart-type fatty acid binding protein (h-FABP) as a target, the constructed PEC sensor showed good stability and selectivity in a biosensing system. Under optimal conditions, the as-prepared sensing platform displayed high sensitivity for h-FABP with a dynamic linear response range of 0.1-1000 pg/mL and a lower detection limit of 55 fg/mL. This research presents the liposome-mediated PEC immunoassay based on in situ type-I heterojunction establishment, providing a new protocol for analyzing various targets of interest.

Liposome-Mediated In Situ Formation of Type-I Heterojunction for Amplified Photoelectrochemical Immunoassay.

Applications of two-dimensional layered nanomaterials in photoelectrochemical sensors: A comprehensive review

Recent advances on signal amplification strategies in photoelectrochemical sensing of microRNAs.

D-A F8BT/g-C3N4 type II heterojunction nanocomposite was employed as photoelectrode material for photoelectrochemical (PEC) aptasensor based on rolling circle amplification (RCA) with the assistance of 3D-printed device for carcinoembryonic antigen (CEA) detection. D-A type F8BT improved photocurrent response of g-C3N4 nanosheet after forming D-A F8BT/g-C3N4 type II heterojunction which effectively constructed built-in electric field and reduced electron-hole recombination. With the introduction of DNA-AuNP probes by π-stacking interaction, the local plasmon resonance (LSPR) of AuNPs enhanced local electric field, promoted the generation of electron-hole and further improved photocurrent response. When target CEA was in presence of sensing platform, sandwich construction was formed between two kinds of CEA aptamers and CEA on magnetic beads, triggering the RCA reaction to produce repeated sequences. Partial sequences of complementary-DNA in combination with RCA results was digested by Exo III enzyme to release signal-DNA, detaching DNA-AuNP probes from the surface of the F8BT/g-C3N4 by complementation, causing the attenuation of LSPR and the decrease of photocurrent response. Combing with 3D-printed device, this PEC aptasensor exhibited a linear response to CEA from 0.02 ng mL−1 to 50 ng mL−1 with detection limit of 6.7 pg mL−1, contributing to develop all organic polymer semiconductors as photoelectric materials in PEC study.

Plasmonic enhanced photoelectrochemical aptasensor with D-A F8BT/g-C3N4 heterojunction and AuNPs on a 3D-printed device

Photoelectrochemical (PEC) biosensors incorporating biomolecular recognition with photon-to-electron conversion capabilities of the photoactive species have been developed for molecular diagnosis, but most involve difficulty in adjusting band gap positions and are unsuitable for PEC biodetection. In this work, an innovative PEC biosensor combined with quantum size-controlled engineering based on quantum confinement by controlling the quantum size was designed for the detection of human papillomavirus-16 (HPV-16) through CRISPR-Cas12a (Cpf1)-induced disassembly of Z-scheme heterojunction. To the best of our knowledge, quantum size-controlled engineering that precisely tunes the properties of photoactive materials is first utilized in the PEC bioanalysis. Based on the quantum size effect, the light absorption efficiency and charge-transfer rate were tuned to suitable levels to obtain the best PEC performance. After incubation with target HPV-16, the binding of Cas12a-crRNA to the target double-stranded DNA (dsDNA) stimulated the activity of indiscriminate cleavage toward single-stranded DNA (ssDNA), resulting in a decrease in photocurrent due to the blocking of electron transfer through the heterojunction. By optimizing experimental conditions, the Z-scheme sensing system exhibited incredible photocurrent response to HPV-16 in the range from 3.0 pM to 600 nM with a detection limit of 1.0 pM. Impressively, the application of the quantum size effect could stimulate more interest in the precise design of band gap structure to improve PEC performance.

Size-Controlled Engineering Photoelectrochemical Biosensor for Human Papillomavirus-16 Based on CRISPR-Cas12a-Induced Disassembly of Z-Scheme Heterojunctions.

Herein, an electrochemical (EC)-photoelectrochemical (PEC) dual-mode biosensor was constructed for cytokeratin 19 fragment 21-1 (CYFRA21-1) assay based on the dual-signaling electrochemical ratiometric strategy and "on-off-on" PEC method. The indium tin oxide (ITO) electrode was modified by 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA)@C60 and gold nanoparticles (Au NPs), and the double-stranded DNA composed of thiol/methylene blue (MB)-labeled single-stranded DNA (ssDNA) (S0-MB) and antibody/ferrocene (Fc)-labeled ssDNA (Ab1-S1-Fc) was immobilized on the Au NPs/PTCDA@C60/ITO electrode via the Au-S bond between Au NPs and thiol of S0-MB. With the help of another antibody-labeled ssDNA (Ab2-S2), the presence of CYFRA21-1 triggered a typical antigen-antibody sandwich immune reaction (Ab1, CYFRA21-1, and Ab2) and proximity hybridization between Ab1-S1-Fc and Ab2-S2. This caused the release of Ab1-S1-Fc from the modified electrode and the change of S0-MB to a hairpin structure, resulting in a decrease (an increase) of the oxidation peak current of Fc (MB) and an increase of the photocurrent due to the enhancing (inhibiting) effect of MB (Fc) on the photoelectric performance of the Au NPs/PTCDA@C60/ITO electrode. Thus, CYFRA21-1 was detected by the developed EC-PEC dual-mode sensing platform sensitively, and the linear response ranges of 0.001-40 ng/mL with a detection limit of 0.3 pg/mL for the EC technique and 0.0001-4 ng/mL with a detection limit of 0.03 pg/mL for the PEC method were obtained. Furthermore, by changing the specific antibodies of disease-related biomarkers, the developed dual-mode biosensing platform could be readily extended to detect other antigens, implying its great potential applications in biological analysis and early disease diagnosis.

Sensitive Dual-Mode Biosensors for CYFRA21-1 Assay Based on the Dual-Signaling Electrochemical Ratiometric Strategy and "On-Off-On" PEC Method.

A novel signal-off photoelectrochemical biosensor for M.SssI MTase activity assay based on GQDs@ZIF-8 polyhedra as signal quencher

As the most important serum biomarker for prostate cancer, sensitive and accurate detection of prostate-specific antigen (PSA) is of great reference value for the clinical diagnosis and treatment of prostate cancer. Herein, a peptide cleavage-mediated and environmentally friendly photocurrent polarity switching system was developed for ultrasensitive and highly selective detection of PSA based on the efficiently switching of photocurrent polarity of silver indium sulfide nanoparticles (AgInS2 NPs)-coated indium tin oxide (ITO) electrode by amino-functionalized CuO cubes (NH2-CuO). The porous CuO cubes were synthesized by calcination of HKUST-1 and functionalized with aminosilane. In the presence of PSA, the biotin and rhodamine B-labeled peptide (Bio-Pep-RhB) was cleaved and part of the peptide (P-Pep-RhB) was obtained by magnetic separation. Through host-guest recognition between β-CD and RhB, the P-Pep-RhB was immobilized on the β-CD/AgInS2 NPs/ITO electrode. Then, the amino-rich sequence on P-Pep-RhB combined with NH2-CuO via glutaraldehyde results in the switch of anodic photocurrent to cathodic photocurrent. On account of the high-efficient peptide cleaving strategy and the new photocurrent polarity switching system of porous CuO cubes//AgInS2 NPs, the prepared sensing platform displayed outstanding analytical performance for PSA with a wide linear response range (0.1 pg mL-1-100 ng mL-1) and a lower detection limit of 0.06 pg mL-1. The proposed analytical method could be easily extended to analyze other proteins via changing the peptide sequence, which has a potential application in the fields of biological analysis and medical diagnosis.

Peptide Cleavage-Mediated and Environmentally Friendly Photocurrent Polarity Switching System for Prostate-Specific Antigen Assay.

Highly sensitive and selective microRNA (miRNA) assay is of great significance for disease diagnosis and therapy. Herein, a magnetic-assisted electrochemistry (EC)-photoelectrochemistry (PEC) dual-mode biosensing platform was developed for miRNA-210 detection based on dual-signaling EC and photocurrent-polarity-switching PEC strategies. Porous magnetic Fe3O4 octahedra with a large surface area were synthesized by calcining Fe-based metal-organic frameworks. Subsequently, the magnetic photoelectric materials (Fe3O4@CdS) were developed by the successive ionic layer adsorption and reaction method in Cd2+ and S2- solutions. Then, the self-assembled DNA nanoprisms contained three thiols/hanging arms that could capture miRNA-210 efficiently and were anchored to the Fe3O4@CdS octahedra via the Cd-S bond. When miRNA-210 was present, the double-stranded DNA concatemers [the self-assembled duplex helixes based on a pair of methylene blue (MB)-labeled single-stranded DNAs (AP1 and AP2) through the hybridization chain reaction and then intercalated with adriamycin (Dox) into their grooves] were connected with the Fe3O4@CdS-DNA nanoprisms. MB and Dox not only acted as the electrochemical probes but also synergistically switched the photocurrent polarity of the Fe3O4@CdS octahedra. Thus, miRNA-210 was assayed sensitively and selectively via the proposed EC-PEC dual-mode biosensing platform. Additionally, the abovementioned recognition steps occurred in a homogeneous system, and the effects of the impurities and interferences on the miRNA-210 assay could be easily avoided by magnetic separation due to the good magnetic properties of Fe3O4 octahedra. The proposed EC-PEC dual-mode biosensing platform showed a wide range of potential applications in bioanalysis and early diagnosis of disease.

Highly Selective and Sensitive microRNA-210 Assay Based on Dual-Signaling Electrochemical and Photocurrent-Polarity-Switching Strategies.

Herein, porous ZrO2 octahedra with uniform size and large surface area were synthesized by direct calcination of zirconium-based metal-organic frameworks (UiO-66) and its photoelectric properties were enhanced by modification with CdS nanoparticles. Based on porous ZrO2/CdS octahedra, a label-free and sensitive photoelectrochemical (PEC) biosensor with near-zero-background noise was proposed for protein kinase A (PKA) activity assay. The PKA-specific peptide was immobilized on the gold nanoparticles-modified indium tin oxide electrode through its cysteine end. With the participation of adenosine triphosphate (ATP), the peptide phosphorylation was catalyzed by PKA and the ZrO2/CdS octahedra were introduced to the electrode via Zr-O-P coordination between ZrO2 and phosphate group on the phosphorylated peptide. Under visible light irradiation, a large anodic photocurrent generated. The developed PEC biosensor had good analytical characteristics for PKA activity assay: near-zero background noise, wide linear range (0.001−100 U mL−1) and low detection limit (0.00035 U mL−1). This strategy provides an efficient avenue for PKA activity assay, and shows great potential application in diagnostics and drug discovery of PKA-related diseases. Moreover, the developed porous ZrO2/CdS octahedra may have a wider application in PEC monitoring of phosphorylation-dephosphorylation processes of proteins and fast PEC assay of organophosphorus pesticides.

Ke Xiao

Papers

Sensitive Dual-Mode Biosensors for CYFRA21-1 Assay Based on the Dual-Signaling Electrochemical Ratiometric Strategy and "On-Off-On" PEC Method.

A novel signal-off photoelectrochemical biosensor for M.SssI MTase activity assay based on GQDs@ZIF-8 polyhedra as signal quencher

Peptide Cleavage-Mediated and Environmentally Friendly Photocurrent Polarity Switching System for Prostate-Specific Antigen Assay.

Highly Selective and Sensitive microRNA-210 Assay Based on Dual-Signaling Electrochemical and Photocurrent-Polarity-Switching Strategies.

A label-free photoelectrochemical biosensor with near-zero-background noise for protein kinase A activity assay based on porous ZrO2/CdS octahedra